Abstract: OBJECTIVE To observe the clinical effect of mupirocin ointment on treatment of skin infections so as to provide guidance for reasonable clinical use of antibiotics. METHODS A total of 150 patients with mild and moderate skin infections who were treated in hospitals from Oct 2014 to Oct 2015 were recruited as the study objects and randomly divided into the observation group and the control group, with 75 cases in each. Both groups were treated with conventional antibiotics, the observation group was given additional mupirocin ointment for smearing of the affected area, three times a day, continuous use for 7 days. The therapeutic effects and clearance rates of pathogens were observed and compared between the two groups of patients, and the statistical analysis of data was performed with the use of SPSS19.0 software. RESULTS Of the pathogens isolated from the 150 patients, there were 62 strains of Staphylococcus aureus, 43 strains of Escherichia coli, 18 strains of Pseudomonas aeruginosa, 10 strains of coagulase-negative Staphylococcus, 9 strains of Streptococcus hemolyticus, and 8 strains of other species of pathogens. Totally 55 (36.66%) patients had surgical trauma, 46 (30.67%) patients had cellulitis, 21 (14.00%) patients had animal bites, 15 (10.00%) patients had diabetic skin ulcers, and 13 (8.67%) patients had other diseases. The effective rate of treatment of the observation group was 97.33%, significantly higher than 86.67% of the control group (P<0.05). The bacterial clearance rate of the observation group was 96.00%, significantly higher than 85.33% of the control group (P<0.05). CONCLUSION The mupirocin ointment can achieve significant clinical effect on treatment of skin infections, with the bacterial clearance rate high.